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Abstract
Grant Number: 1R03MH084103-01 Project Title: Identification of Inhibitors of the Plasmodium Falciparum M18 Metalloprotease
PI Information: Name Title DALTON, JOHN PIUS. GARDINER, DONALD L. (Contact) dong@qimr.edu.au GREMBECKA, JOLANTA TRENHOLME, KATHARINE RUTH. Abstract: DESCRIPTION (provided by applicant): Malaria remains a significant cause of morbidity and mortality worldwide with an estimated 2 million people dying from this disease every year. The majority are children under 5 living in Sub-Saharan Africa. Drug resistance to the commonly available drugs is widespread, and with a safe and effective vaccine still many years away, new chemotherapeutic agents are required to ensure that cheap and effective treatment can be maintained. The M18 class of metalloproteases are involved in the catabolism of proteins. In the apicomplexan parasite of the genus Plasmodium the causative agent of malaria, this key enzyme is involved with hemoglobin digestion. Using an antisense transgenic approach we have shown that it is possible to selectively target this enzyme. This leads to a lethal phenotype. We have generated a recombinant protein to this enzyme that is suitable for adaptation to high throughput screening. This will lead to the identification of new and novel compounds that can target this enzyme.
Public Health Relevance: Project Narrative Malaria is the third leading cause of death due to an infectious disease. This proposal seeks to identify new chemotherapeutic agents to help combat this disease.
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Institution: QUEENSLAND INSTITUTE OF MEDICAL RESEARCH 300 Herston Road BRISBANE, 4006 Fiscal Year: 2008 Department: Project Start: 04-JUN-2008 Project End: 31-MAY-2009 ICD: NATIONAL INSTITUTE OF MENTAL HEALTH IRG: ZMH1